Uterine leiomyomas (ULM) are a common cause of solid pelvic tumors in women. Their etiopathogenesis remains unclear. Interleukins (ILs) and their receptors can influence tumor biology of ULM. The aim ...of this study was to evaluate single nucleotide polymorphisms (SNPs) exhibited in the genes
(rs2070874),
(rs1801275),
(rs11575934),
(rs6887695),
(rs20541) and
(rs7517847) as risk factors for ULM in Slovenian women and to identify associations between corresponding clinical parameters and the analyzed SNPs. In addition, solitary and multiple ULM were compared to identify clinical and/or genetic parameters influencing their occurrence. We conducted a case-control study that included 181 women with leiomyomas and 133 control subjects. Genotyping of selected SNPs was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and high resolution melting (HRM) techniques. The TT genotype of rs20541 (
) was significantly associated with decreased risk of ULM compared to both the CC and CT genotypes
0.018; odds ratio (OR) = 0.184; 95% confidence interval (95% CI) = 0.048-0.7121. Using genetic and clinical data to develop a predictive model with logistic regression, we found that adenomyosis, higher age at diagnosis, family history of ULM occurrence, earlier menarche, lower number of pregnancies and lower age at first sexual intercourse, the G allele and genotypes AG and GG of rs1801275 (
) were associated with an increased risk of multiple ULM occurrence. We also found an association between rs20541 (
) and 17ß-estradiol serum levels in patients with multiple ULM (
0.003). Our study showed, for the first time, that rs20541 (
) may contribute to susceptibility of ULM development and that rs1801275 (
) can predispose patients to develop multiple ULM.
Recent genome-wide association studies linked childhood asthma with single-nucleotide polymorphisms (SNPs) in ORM1-like protein 3 (ORMDL3) gene region on chromosome 17q21. We analyzed the effect of ...functional SNP rs2872507 in ORMDL3 gene region on the response to antiasthmatic treatment with inhaled corticosteroids (ICSs) and ORMDL3 gene expression. Forced expiratory volume in 1 s increased significantly by 13.3% of predicted value after therapy in atopic asthmatics with AA genotype, compared with 7.0% in heterozygotes and 4.9% increase in GG homozygotes (P=0.0176). Median relative expression of ORMDL3 gene in asthmatics with AA, AG and GG genotypes was 0.75, 1.05 and 1.21, respectively (P<0.0001). Treatment with ICSs was significantly associated with the increase of median relative expression of ORMDL3 gene, from 0.88 to 1.21 (P=0.0032) in atopic asthmatics. Our results suggest that rs2872507 is associated with ORMDL3 gene expression and with ICS treatment response in children with atopic asthma.
We used coding and noncoding polymorphisms evenly spaced across the ABCB1/MDR1 gene to perform association analysis in Slovenian patients with inflammatory bowel diseases and to obtain haplotype ...structure and patterns of linkage disequilibrium (LD) in the MDR1 gene. A disease association study was performed in 307 IBD patients, including 144 patients with ulcerative colitis (UC) and 163 patients with Crohn's disease (CD), and 355 healthy controls. Here we report an association between MDR1 alleles, polymorphisms and haplotypes and refractory CD patients, who do not respond to standard therapy, including patients who develop fistulas. We also report an association with UC and MDR1 polymorphisms in a Slovenian population. Haplotypes significantly associated with diseases were defined by single-nucleotide polymorphisms (SNPs) in exons 12 (1236 C>A), 21(A893S), and 26 (3435 C>T). In addition, two intronic SNPs in LD with the disease haplotype, one in intron 13 (rs2235035) and another in intron 16 (rs1922242), were significantly associated with refractory Crohn (P=0.026, odds ratio (OR) 2.7 and P=0.025, OR 2.8, respectively), as well as with UC (P=0.006, OR 1.8 and P=0.026, OR 1.9, respectively). Our results suggest that MDR1 is a potential target for therapy in refractory CD patients and in patients with UC.
Summary
Background
Inhaled corticosteroids (ICS) are the most widely prescribed and effective medication to control asthma symptoms and exacerbations. However, many children still have asthma ...exacerbations despite treatment, particularly in admixed populations, such as Puerto Ricans and African Americans. A few genome‐wide association studies (GWAS) have been performed in European and Asian populations, and they have demonstrated the importance of the genetic component in ICS response.
Objective
We aimed to identify genetic variants associated with asthma exacerbations in admixed children treated with ICS and to validate previous GWAS findings.
Methods
A meta‐analysis of two GWAS of asthma exacerbations was performed in 1347 admixed children treated with ICS (Hispanics/Latinos and African Americans), analysing 8.7 million genetic variants. Those with P ≤ 5 × 10−6 were followed up for replication in 1697 asthmatic patients from six European studies. Associations of ICS response described in published GWAS were followed up for replication in the admixed populations.
Results
A total of 15 independent variants were suggestively associated with asthma exacerbations in admixed populations (P ≤ 5 × 10−6). One of them, located in the intergenic region of APOBEC3B and APOBEC3C, showed evidence of replication in Europeans (rs5995653, P = 7.52 × 10−3) and was also associated with change in lung function after treatment with ICS (P = 4.91 × 10−3). Additionally, the reported association of the L3MBTL4‐ARHGAP28 genomic region was confirmed in admixed populations, although a different variant was identified.
Conclusions and clinical relevance
This study revealed the novel association of APOBEC3B and APOBEC3C with asthma exacerbations in children treated with ICS and replicated previously identified genomic regions. This contributes to the current knowledge about the multiple genetic markers determining responsiveness to ICS which could lead in the future the clinical identification of those asthma patients who are not able to respond to such treatment.
Early identification of children with poorly controlled asthma is imperative for optimizing treatment strategies. The analysis of exhaled volatile organic compounds (VOCs) is an emerging approach to ...identify prognostic and diagnostic biomarkers in pediatric asthma.
To assess the accuracy of gas chromatography-mass spectrometry based exhaled metabolite analysis to differentiate between controlled and uncontrolled pediatric asthma.
This study encompassed a discovery (SysPharmPediA) and validation phase (U-BIOPRED, PANDA). Firstly, exhaled VOCs that discriminated asthma control levels were identified. Subsequently, outcomes were validated in two independent cohorts. Patients were classified as controlled or uncontrolled, based on asthma control test scores and number of severe attacks in the past year. Additionally, potential of VOCs in predicting two or more future severe asthma attacks in SysPharmPediA was evaluated.
Complete data were available for 196 children (SysPharmPediA=100, U-BIOPRED=49, PANDA=47). In SysPharmPediA, after randomly splitting the population into training (n=51) and test sets (n=49), three compounds (acetophenone, ethylbenzene, and styrene) distinguished between uncontrolled and controlled asthmatics. The area under the receiver operating characteristic curve (AUROCC) for training and test sets were respectively: 0.83 (95% CI: 0.65-1.00) and 0.77 (95% CI: 0.58-0.96). Combinations of these VOCs resulted in AUROCCs of 0.74 ±0.06 (UBIOPRED) and 0.68 ±0.05 (PANDA). Attacks prediction tests, resulted in AUROCCs of 0.71 (95% CI 0.51-0.91) and 0.71 (95% CI 0.52-0.90) for training and test sets.
Exhaled metabolites analysis might enable asthma control classification in children. This should stimulate further development of exhaled metabolites-based point-of-care tests in asthma.
Molecular based differentiation of various bacterial species is important in phylogenetic studies, diagnostics and epidemiological surveillance, particularly where unusual phenotype makes the ...classical phenotypic identification of bacteria difficult. Molecular approach based on the sequence of 16S ribosomal RNA gene analysis can achieve fast and reliable identification of bacteria. High resolution melting (HRM) curve analysis has been developed as an attractive novel technique for DNA sequence discrimination but it's application for bacteria differentiation has not been well studied yet. We have developed HRM assay for differentiation of sixteen pathogenic or opportunistic bacterial species. Amplified partial 16S ribosomal RNA gene region between 968 and 1401 positions (E. coli reference numbering) was subsequently used in high resolution melting curve analysis of PCR products for bacterial species differentiation. Sixteen bacterial species were simultaneously discerned by difference plot of normalized and temperatures shifted melting curves, without need for spiking of DNA, hetero-duplexing experiments or application of several primer pairs. High resolution melting curve analysis of duplex DNA is simple, fast and reliable tool for bacterial species differentiation and may efficiently complement phenotypic identification of bacteria.
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